With this new Senior Research Award (K05), the principal investigator will continue to pursue her clinical research career goal of improving the treatment of alcohol dependence by 1) integrating three domains of clinical research; psychotherapeutic interventions, pharmacotherapy development, human bio-behavioral laboratory studies, 2) training new clinical researchers, and 3) educating the treatment community about new treatments. She will also conduct research on alcohol and tobacco interactions. In order to sustain her performance as a leader in clinical research and psychopharmacology, she will continue extensive collaborations in interdisciplinary research. Continued scientific growth will benefit as well from activities related to mentoring and participation in research review and advisory group participation. The research plan is focused on the COMBINE Study. Plans for future research include using human laboratory paradigms to screen new medications for alcohol dependence and to take these into clinical trials. The COMBINE study is a NIAAA sponsored multi-site clinical trial designed to answer questions about the benefits of combining behavioral and pharmacological interventions. Two medications, naltrexone and acamprosate, have shown promise in reducing relapse to heavy drinking and improving abstinence in a number of U.S. and European clinical trials. The two behavioral treatments, Medical Management (MM) and Combined Behavioral Intervention (CBI), have potential to be valuable adjuncts to pharmacotherapy. MM appears to be cost-effective and suitable for delivery in primary care or managed care settings by non-specialists. The primary hypothesis is that combining the two medications (naltrexone and acamprosate) with a moderate intensity behavioral treatment (CBI) will yield better outcomes than less intensive approaches (e.g., placebo and MM; acamprosate or naltrexone and MM) for alcohol dependent patients. A total of 1375 subjects from 11 clinical sites comprise the targeted sample for this 16 week trial with long-term follow-up. Individuals meeting study criteria are randomly assigned to one of nine pharmacological (naltrexone and acamprosate) and behavioral treatment (MM and CBI) combinations to form a complete 2X2X2 factorial design. A ninth cell is included to test the efficacy of CBI without "pills." Ultimately, the results of this study will have important implications for the treatment of alcoholism in the United States.